The long term goal of this project is to gain a comprehensive understanding of the intimate associations of larval digenetic trematodes and gastropod mollusks. Larval digeneans and their secretory-excretory products (SEP) will be used as probes to understand how the molluscan internal defence system (IDS) recognizes and responds to intruders. Strategies employed by larval digeneans in subverting the molluscan IDS will also be investigated. In the process, a broader understanding of host-parasite associations and the evolution of internal defence systems will be gained. This project will also contribute information of potential relevance to the development of novel methods for controlling human schistosomes. Using the snail Biomphalaria glabrata and the trematode Echinostroma paraensei as primary model systems, the functional role of snail hemolymph polypeptides known to increase in abundance following infection and to precipitate parasite antigens will be studied. The gene encoding this parasite responsive molecule will be identified and characterized and its possible homology with other molecules assessed. Also, specific molecules within E. paraensei sporocyst SEP that directly affect the functional integrity of B. glabrata hemocytes will be identified. The genes producing relevant SEP components will be identified, sequenced and compared to other known genes. A series of studies is also proposed to determine if SEP has cytotoxic or mitogenic effects for hemocyte structure. A panel of six digenean and four snail species will be investigated to determine if SEP from each parasite specifically affects only hemocytes of compatible snails, and if parasites are more likely to be bound by hemocytes from incompatible than compatible snail hosts. This comparative study will serve to check the validity of results obtained with commonly-studied model systems, and will help to elucidate fundamental principles underlying the phenomenon of host specificity. Finally, using genes outlined in the above studies, the genomes of the six trematode and four snail species will be probed in search of related genes.